Association between parabens exposure and neurodevelopment in children.

OBJECTIVE: Parabens are a group of substances commonly employed as antimicrobial preservatives. The effect of parabens on the development of neurotoxicity in children is still controversial. This study aimed to explore the associations between parabens exposure and children's neurodevelopmental performance, emphasizing potential sex differences and the combined effects of parabens. METHODS: We used the long-term follow-up study of Taiwanese generation, Taiwan Birth Panel Study II (TBPS II). We recruited the group of children at 6-8 years old. And, we measured parabens in children urine, including methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP). Children's attention-related performance was evaluated using the Conners Kiddie Continuous Performance Test 2nd Edition (K-CPT 2). The study employed both linear regression and mixture analysis quantile g-computation (QGC) methods to discern associations. A stratified analysis by sex and QGC was implemented to delve deeper into the cumulative effects of parabens. RESULTS: A total of 446 subjects completed both the parabens analysis and the K-CPT 2 survey. The overall association between parabens and neurodevelopmental performance was not pronounced, but discernible sex differences emerged. In the single pollutant analysis, elevated PP concentrations were associated with higher K-CPT 2 scores particularly in detectability (d') (ß = 0.92 [95 % CI = 0.15 to 1.69]) and commissions (ß = 0.95 [95 % CI = 0.12 to 1.78]), among girls. Further, in the mixture analysis, a significant association between PP and detectability (d') was observed in girls (ß = 1.68 [95 % CI = 0.11 to 3.26]). CONCLUSIONS: This study identified sex-specific associations between parabens and attention performance. Consistent outcomes across single and mixture analysis methods. Further research is crucial to clarify these causal associations.

Association between Cesarean section delivery and increased risk of childhood Kawasaki disease.

AIM: Cesarean section delivery is associated with microbiota disruption and immuno-dysregulation during childhood, but the association with Kawasaki disease remains uncertain. We aimed to evaluate the association between Cesarean section and Kawasaki disease. METHODS: We examined the association between Kawasaki disease between six and eighteen months and Cesarean section within a birth cohort of 15,796 mother-infant pairs in Taiwan. The associations were assessed with Poisson regression in the study population, in the 1:2 propensity score-matched subpopulation, and compared with febrile convulsion, trauma and accidents during the same interval as negative control outcomes. RESULTS: Cesarean section was found to increase the risk of Kawasaki disease among overall population (adjusted relative risk [aRR]: 2.22, 95 % confidence interval (CI): 1.14-4.34) and the matched subpopulation (aRR: 2.29, 95 % CI: 1.14-4.68 in PS-matched subpopulation). Meanwhile, there was no association between Cesarean section and the clinic visits for febrile convulsion, trauma and accidents. CONCLUSION: In conclusion, this study identified a potential association between Cesarean section delivery and a higher risk of Kawasaki disease during six-to eighteen months of the prospective birth cohort in Taiwan.

Precocious puberty in patients with Pompe disease.

Introduction: The life expectancy of Pompe disease patients has increased due to improved neonatal screening and enzyme replacement therapy. Nevertheless, the potential effect of frequent medical device exposure on pubertal development in these patients is not well understood, so further investigation is warranted. Methods: In this cross-sectional study, we assessed the growth and puberty of nine Pompe disease patients. In addition, to determine the effects of frequent plastic medical device exposure in these patients, we measured urinary phthalate metabolites before and one day after enzyme replacement therapy. Results: Five out of nine patients (55%) with Pompe disease on enzyme replacement therapy had precocious puberty. Patients with precocious puberty had significantly shorter predicted adult heights compared to those with normal puberty (p = 0.014). The levels of mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) increased after enzyme replacement therapy, but the average levels of phthalate metabolites did not significantly differ between patients with normal and precocious puberty. Conclusion: Pompe disease patients on enzyme replacement therapy tend to have precocious puberty, which may reduce their adult height. There are no significant differences in urinary phthalate metabolites between normal and precocious puberty patients. Regular follow-up of growth and puberty in Pompe disease patients is important to improve their health outcomes.

Identification of serum metabolic signatures of environmental-leveled phthalate in the Taiwanese child population using NMR-based metabolomics.

Phthalates have become important environmental pollutants due to their high exposure frequency in daily life; thus, phthalates are prevalent in humans. Although several epidemiologic surveys have linked phthalates with several adverse health effects in humans, the molecular events underlying phthalate exposure have not been fully elucidated. The purpose of this study was to reveal associations between phthalate exposure and the serum metabolome in Taiwanese children using a metabolomic approach. A total of 256 Taiwanese children (8-10 years old) from two cohorts were enrolled in this study. Twelve urinary phthalate metabolites were analyzed by high-performance liquid chromatography/tandem mass spectrometry, while a nuclear magnetic resonance-based metabolomic approach was used to record serum metabolic profiles. The associations between metabolic profiles and phthalate levels were assessed by partial least squares analysis coupled with multiple linear regression analysis. Our results revealed that unique phthalate exposures, such as mono-isobutyl phthalate, mono-n-butyl phthalate, and mono (2-ethyl-5-oxohexyl) phthalate, were associated with distinct serum metabolite profiles. These phthalate-mediated metabolite changes may be associated with perturbed energy mechanisms, increased oxidative stress, and lipid metabolism. In conclusion, this study suggests that metabolomics is a valid approach to examine the effects of environmental-level phthalate on the serum metabolome. This study also highlighted potentially important phthalates and their possible effects on children.

Association between maternal shift work during pregnancy child overweight and metabolic outcomes in early childhood.

Background: Previous studies found that maternal shift work during pregnancy was associated with many reproductive hazards, including small for gestational age, preterm birth, stillbirth, and neurodevelopmental impairment. Some studies also showed that these children are more likely to become overweight in early childhood. However, the association with metabolic factors, such as insulin resistance and dyslipidemia, was less studied. Hence, we aimed to understand better the relationship between maternal shift work during pregnancy and the risk of childhood overweight and metabolic outcomes. Confounding factors were also discussed, including diet, exercise, and demographical factors. Methods: We enrolled pregnant women before delivery in the Taiwan Birth Panel Study (TBPS) II conducted between 2010 and 2012, and followed the children of these participants in 2018. The objective of this study is to investigate the influence of prenatal and postnatal factors on infant and early childhood health. During the follow-up in 2018, we checked children's demographic data, obtained blood specimens, and checked their blood sugar, blood insulin, and lipid profiles. Structured questionnaires were used to evaluate demographic data. Multiple linear and logistic regressions were used to examine the associations between maternal shift work during pregnancy and child overweight, metabolic disorders, such as HOMA-IR, and lipid profiles. Results: In this study, we included 407 mother-children pairs with different work shifts (350 day workers and 57 shift workers), and a sub-population without underweight children was also created (290 day workers and 47 shift workers). Shift work during pregnancy was associated with a higher Homeostasis Model Assessment-Insulin Resistance index (HOMA-IR) and a higher odds ratio for overweight in children born from mothers doing shift work during pregnancy after adjustment. The findings were attenuated when we investigated the effect of shift work before pregnancy. Conclusion: Our study suggested that maternal shift work during pregnancy was associated with child overweight and insulin resistance in early childhood.

Prevalence of exposure to benzodiazepines among pregnant women in Taiwan: A nationwide longitudinal study.

Although more than one hundred studies have examined the prevalence of the use of benzodiazepines and benzodiazepine-like Z-hypnotics (BZDs) among pregnancy events, further analysis of the effects of dosage or type of BZDs is needed. The aim of this study was to examine the prevalence rate of BZDs use in pregnancy events, stratified by trimester over time, with characteristics of the dosage and type of BZDs. This is a retrospective population study based on linking three national databases. We examined the prevalence rates from 2004 to 2017, and contrasted the results based on >0 defined daily dose (DDD) and ≥0.5 DDD. We identified 2,630,944 pregnancy events with live births; 89,897 (3.4%) of the associated pregnancy events had used some form of BZD during pregnancy. The prevalence of BZDs use, as defined by >0 DDD, decreased from 4.1% in 2004 to 2.9% in 2017, indicating a decrease in sporadic use and an increase in stable use within therapeutic doses. Meanwhile, BZDs use defined by ≥0.5 DDD increased from 0.1% in 2004 to 0.4% in 2017. Zolpidem was the most frequently prescribed BZDs, as defined by >0 DDD or ≥0.5 DDD. This national cohort study demonstrates the importance of average dosage in the definition of BZDs use in pregnancy events, and it found opposite trends in the prevalence of use between different dosages.

Intravitreal Bevacizumab Is Associated With Prolonged Ventilatory Support in Preterm Infants With Bronchopulmonary Dysplasia.

BACKGROUND: Intravitreal bevacizumab (IVB), an anti-vascular endothelial growth factor (VEGF) antibody, is a widely adopted treatment for retinopathy of prematurity (ROP). Although animal studies have demonstrated that IVB inhibits alveologenesis in neonatal rat lung, the clinical influence of IVB on respiratory outcomes has not been studied. RESEARCH QUESTION: Does IVB affect the respiratory outcome in preterm infants with bronchopulmonary dysplasia? STUDY DESIGN AND METHODS: We retrospectively assessed very low birth weight (VLBW) preterm infants admitted to our neonatal ICU between January 2016 and June 2021. Furthermore, we evaluated the short-term respiratory outcomes after IVB therapy in VLBW preterm infants requiring ventilatory support at 36 weeks' postmenstrual age (PMA). RESULTS: One hundred seventy-four VLBW preterm infants with bronchopulmonary dysplasia were recruited. Eighty-eight infants showed ROP onset before being ventilator free, and 78 infants received a diagnosis of the most severe ROP before being ventilator free. Among them, 32 received a diagnosis with type 1 ROP and received IVB treatment. After adjusting for gestational age, birth body weight, and baseline respiratory status, we discovered that IVB is associated significantly with prolonged ventilatory support and a lower likelihood of becoming ventilator free (hazard ratio, 0.53; P = .03). INTERPRETATION: IVB may have a short-term respiratory adverse effect in patients requiring ventilatory support at 36 weeks' PMA. Therefore, long-term follow-up for respiratory outcomes may be considered in VLBW infants who receive IVB treatment.

Lipid responses to environmental perfluoroalkyl substance exposure in a Taiwanese Child cohort.

Although recent epidemiologic studies have focused on some of the health effects of perfluoroalkyl substance (PFASs) exposure in humans, the associations between PFASs exposure and the lipidome in children are still unclear. The purpose of this study was to assess lipid changes in children to understand possible molecular events of environmental PFASs exposure and suggest potential health effects. A total of 290 Taiwanese children (8-10 years old) were included in this study. Thirteen PFASs were analyzed in their serum by high-performance liquid chromatography-tandem mass spectrometry (LC-MS). MS-based lipidomic approaches were applied to examine lipid patterns in the serum of children exposed to different levels of PFASs. LC coupling with triple quadrupole MS technology was conducted to analyze phosphorylcholine-containing lipids. Multivariate analyses, such as partial least squares analysis along with univariate analyses, including multiple linear regression, were used to analyze associations between s exposure and unique lipid patterns. Our results showed that different lipid patterns were discovered in children exposed to different levels of specific PFASs, such as PFTrDA, PFOS, and PFDA. These changes in lipid levels may be involved in hepatic lipid metabolism, metabolic disorders, and PFASs-membrane interactions. This study showed that lipidomics is a powerful approach to identify critical PFASs that cause metabolite perturbation in the serum of children and suggest possible adverse health effects of these chemicals in children.

Associations Between Infant Developmental Delays and Secondhand Smoke Exposure Modified by Maternal Prepregnancy Overweight and Obesity Status.

INTRODUCTION: Secondhand smoke exposure during pregnancy has long been associated with adverse health outcomes in children, but only a few studies have examined its effect modifiers. In this study, we applied effect modification analysis for maternal prepregnancy weight status on detrimental neurodevelopmental effect of secondhand smoke exposure during pregnancy and infancy in a nationwide representative population. AIMS AND METHODS: Term singleton mother-infant pairs with nonsmoking mothers were included for main analysis (N = 15 987) from the Taiwan Birth Cohort Study (TBCS), and were further matched with propensity score (n = 5434). We extracted secondhand smoke exposure during pregnancy and infancy, and eight neurodevelopmental milestones from the responses in the baseline visit at 6 months, and 18-month follow-up of TBCS. The associations between secondhand smoke exposure and neurodevelopmental achievement were analyzed with multivariable logistic regression and Cox model. Propensity score weighting and matching were applied for high-versus-low analysis, and relative excess risk due to interaction were used to estimate effect modification. RESULTS: Higher secondhand smoke exposure was associated with increased likelihood of delayed milestone achievement across gross motor, fine motor, language-related, and social-related domains. The associations in fine motor domains remained observable in propensity score-weighted and -matched models. We identified additive interaction with self-reported maternal overweight and obesity status before pregnancy in milestone development for walking with support, scribbling, and waving goodbye. CONCLUSIONS: Secondhand smoke exposure during pregnancy and infancy were associated with delayed neurodevelopmental milestone achievement at 18 months, and the associations were modified by maternal prepregnancy overweight and obesity status. IMPLICATIONS: The study results suggested the association between maternal secondhand smoke exposure during pregnancy and infancy and delayed fine motor and language-related milestone achievement at 18 months in multivariable, propensity score weighting, and matching populations. The results of positive effect modifications for maternal prepregnancy overweight and obesity status suggested the importance of concurrent interventions on smoke-free environment and maternal health during pregnancy.

Association between short-term exposure to air pollution and sudden infant death syndrome.

The association between air pollution and infant mortality has been inconsistently reported. A few studies have estimated short-term effects of air pollution on infants' health. This population-based case-control study aimed to examine the potential effects of air pollution on sudden infant death syndrome (SIDS) in the post-neonatal period in Taiwan during 1997-2002. Each case of infant death was matched with 20 randomly selected sex-matched controls who were born on the same day and were still alive. We obtained 24-h measurements of air pollutants and meteorological factors in each case and control with 1- to 14-day lags from 55 air-quality monitoring stations. After controlling for potential confounders, conditional logistic regression analysis was performed to estimate effects of air pollutants on SIDS (n = 398) and respiratory death (n = 121) among neonates. In single- and multi-pollutant models, we found that 100-ppb increment in carbon monoxide (Odds Ratio = 1.04-1.07) and 10-ppb increment in nitrogen dioxide (Odds Ratio = 1.20-1.35) with 1- to 14-day lags were associated with significant increase in SIDS, although a significant relationship between air pollution and respiratory death was not determined in 1- to 14-day lags. Short-term carbon monoxide and nitrogen dioxide exposure were associated with significant increase in SIDS in the post-neonatal period, with latency estimated within days before death.

Associations between household incense burning and delayed motor development among preterm infants modified by gestational age and maternal educational status.

BACKGROUND: Household incense burning is a common ritual behavior in the Asia-Pacific region but has been associated with inferior developmental outcomes in term infants. We aimed to examine these associations among preterm infants. METHODS: Information from 1190 mother-infant pairs during 6- and 18-month follow-up to the Taiwan Birth Cohort Study was examined for associations between household incense burning exposure and infant neurodevelopmental milestone achievement using multivariable Cox proportional hazard model with propensity score weighting, along with stratified, sensitivity, and decomposition analysis. RESULTS: Household incense burning exposure was associated with delayed gross motor milestone achievement among all preterm infants according to the Cox model and after propensity score weighting. Meanwhile, associations for delayed development were found in gross motor domain milestones among late preterm infants, while fine motor domain delay was found among other preterm infants. Furthermore, the associations between household incense burning status and gross motor milestone delays were attenuated by the interaction between higher education level and household incense burning exposure status. CONCLUSIONS: Household incense burning exposure was associated with delays, and the motor domains affected differed according to degree of prematurity. These associations were modified by the attenuation upon higher maternal educational status and exposure status interaction.

Intrauterine exposure to per- and polyfluoroalkyl substances may harm children's lung function development.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA), are common persistent environmental organic pollutants. Animal studies have indicated that PFAS influence inflammatory responses and lung development. However, whether prenatal or childhood PFAS exposure affects children's lung function remains unclear. This study aimed to investigate both in utero exposure and childhood exposure to PFAS and the relationships between them and lung function development in childhood. METHODS: In total, 165 children were recruited from the Taiwan Birth Panel Study (TBPS). Cord blood plasma and children's serum were collected when they were eight years old. PFAS levels were analysed by ultra-high-performance liquid chromatography/tandem mass spectrometry. When these children reached eight years of age, we administered detailed questionnaires and lung function examinations. RESULTS: The mean concentrations of PFOA, PFOS, PFNA and PFUA in cord blood among the 165 study children were 2.4, 6.4, 6.0, and 15.4 ng/mL, respectively. The mean concentrations in serum from eight-year-olds were 2.7, 5.9, 0.6, and 0.3 ng/mL, respectively. At eight years of age, the mean FEV1 (forced expiratory volume per sec), FVC (forced vital capacity), PEF (peak expiratory flow) and FEV1/FVC values were 1679 mL, 1835 mL, 3846 mL/s and 92.0%, respectively. PFOA, PFOS, PFNA and PFUA levels in cord blood were inversely associated with FEV1, FVC and PEF values. The PFOS concentration in cord blood was the most consistently correlated with decreasing lung function before and after adjusting for confounding factors. The PFOS concentration was also significantly inversely correlated with lung function in subgroups with lower birth weight and allergic rhinitis. CONCLUSIONS: Our cohort study revealed that the concentrations of PFOA, PFOS, PFNA and PFUA were higher in cord blood than in serum from eight-year-olds. Some trends were also noted between intrauterine PFOS exposure and children's decreasing FEV1, FVC and PEF, especially in subgroups with lower birth weight and allergic rhinitis. Therefore, intrauterine PFAS exposure, especially PFOS, may play a vital role in lung development.

Association between exposure to perfluoroalkyl substances and metabolic syndrome and related outcomes among older residents living near a Science Park in Taiwan.

Perfluoroalkyl substances (PFASs) are an emerging class of artificial environmental chemicals that have multiple potentially harmful effects on health. The largest Science Park in Taiwan discharges wastewater containing PFASs into the Keya River, and a high concentration of PFASs has been found in this river and its aquatic creatures. We conducted a cross-sectional study from 2016 to 2017 of 397 subjects aged 55-75 years living near the river and evaluated the association of PFASs with metabolic syndrome and related outcomes. The results indicated that perfluorooctane sulfonate (PFOS) levels were positively associated with serum low-density lipoprotein (LDL) levels (P for trend = 0.03) and that perfluorononanoic acid (PFNA) and PFOS levels were positively correlated with uric acid levels (P for trend = 0.03 and 0.03). Perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUnDA) levels were negatively associated with serum triglyceride levels (P for trend = 0.014 and < 0.01). After excluding lipid-lowering drug users, the association between certain PFAS levels and the LDL level was significantly enhanced, but the downward trends of serum triglyceride levels were weakened. When stratified by sex, PFNA (P for trend <0.01), perfluorohexanesulfonate (PFHxS) (P for trend <0.01), and PFOS (P for trend <0.01) showed positive associations with the uric acid level only among males. In conclusion, our results showed that associations were consistently null between PFASs and metabolic syndrome. PFAS levels were associated with serum lipids, and lipid-lowering drugs may interfere with this relationship. Certain PFASs were found to be positively associated with uric acid levels, especially in males. Further studies are warranted to clarify the causal relationships.

Time-dependent associations between presentation-based infections and subsequent risk of childhood immune cell malignancies.

BACKGROUND: Infection is hypothesised as a contributory cause of childhood immune cell malignancies. Although some have reported associations between individual infections and immune cell malignancies, some could be spurious due to infections caused by malignancies that were already active prior to diagnosis. METHODS: Identified from Taiwan Cancer Registry, ∼3000 children with four commonest immune cell malignancies diagnosed during 2001-2015 at age 1-20 years were identified and matched with 1:10 controls. Using logistic regression, we estimated the time-specific case-versus-control odds ratios of seven common infection presentations in their health records. We also compared recorded unexplained lymph nodes between cases and controls to explore for how long malignancy may be active prior to diagnosis. RESULTS: Unexplained lymph nodes were increasingly recorded months before the diagnosis of childhood leukaemias and years before the diagnosis of childhood lymphomas. When using p < 0.01 as a guide, large case-control differences in infection records were found mostly within 0-2 months prior to the diagnosis (15 out of 28 comparisons). Changes in odds ratios within 3-35 months (2 out of 28 comparisons) and case-control differences beyond 36+ months prior to diagnosis (7 out of 28 comparisons) was relatively small (∼10 % difference in leukaemias). Statistical power varied according to incidence of malignancy, incidence of infection records, and the age distribution. CONCLUSION: Immune cell malignancies were likely to be active some time before the diagnosis. Previous studies using conventional population-based methods may not be able to distinguish any small causal link between infection and immune cell malignancies from spurious associations.

Maternal exposure to air pollution and the risk of small for gestational age in offspring: A population-based study in Taiwan.

BACKGROUND: Exposure to air pollution has been associated with a wide range of adverse health effects; however, few studies addressed the relationship between ambient particulate matter as well as the compositions in particulate matter such as lead and the risk of small for gestational age (SGA) in offspring. The aim of this study is to investigate the effect of maternal exposure to criteria air pollutants and the lead in total suspended particulate matter during pregnancy on SGA births in Taiwan. METHODS: This population study consisted of 322,513 singleton live births in Taiwan between 1996 and 2002. Daytime (7 AM-7 PM) exposure to particulate matter ≤10 µm (PM10), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3), and monthly exposure to lead in total suspended particles (TSP) during each trimester were estimated. Generalized additive model (GAM) was used to assess the association between maternal exposure to particulate air pollutants and SGA births, taking into account potential confounders and gaseous air pollutants. RESULTS: We found significant association between the highest quartile (≥75th) of maternal PM10 exposure and SGA and demonstrated a significant exposure-response relationship. Furthermore, the highest quartile (≥75th) of maternal lead exposure was also associated with SGA during the second and third trimester of pregnancy, and there was a significant exposure-response relationship between maternal lead exposure and SGA during pregnancy. CONCLUSION: Maternal exposure to PM10 and lead in total suspended particulate matter during pregnancy was associated with an increased risk of SGA in offspring.

Children's environmental health based on birth cohort studies of Asia (2) - air pollution, pesticides, and heavy metals.

The life style and child raising environment in Asia are quite different compared with Western countries. Besides, the children's environmental threats and difficulties in conducting studies could be different. To address children's environmental health in Asia area, the Birth Cohort Consortium of Asia (BiCCA) was co-established in 2011. We reviewed the mercury, polychlorinated biphenyls, perfluoroalkyl substances, phthalates, and environmental tobacco smoke in pervious based on birth cohort studies in Asia. The aim of this study was to summarize the traditional environmental pollution and the target subjects were also based on the birth cohort in Asia area. Environmental pollutants included air pollutants, pesticides focusing on organochlorine pesticides, diakylphosphates, and pyrethroid, and heavy metals including lead, arsenic, cadmium, manganese, vanadium, and thallium. Fetal growth and pregnancy outcomes, childhood growth and obesity, neurodevelopment and behavioral problems, and allergic disease and immune function were classified to elucidate the children's health effects. In total, 106 studies were selected in this study. The evidences showed air pollution or pesticides may affect growth during infancy or childhood, and associated with neurodevelopmental or behavioral problems. Prenatal exposure to lead or manganese was associated with neurodevelopmental or behavioral problems, while exposure to arsenic or cadmium may influence fetal growth. In addition to the harmonization and international collaboration of birth cohorts in Asia; however, understand the whole picture of exposure scenario and consider more discipline in the research are necessary.

Comparison of Nonpolio Enteroviruses in Children With Herpangina and Hand, Foot and Mouth Disease in Taiwan.

BACKGROUND: Nonpolio enterovirus (NPEV) infections are often present with herpangina (HA) and hand, foot and mouth disease (HFMD). Most countries sample NPEVs in HFMD cases, targeting enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) that are associated with outbreaks and severe complications. HA is also monitored in Taiwan and several other countries, but its viral characteristics are underreported. METHODS: Through Taiwan's National Virologic Surveillance, information regarding ~100,000 child respiratory samples (2002-2015) was linked to concurrent (0-6 days before the sampling date) outpatient records from the National Health Insurance databases, including ~15,000 HA-related and ~7000 HFMD-related samples. We assessed sample representation and NPEV positive rates, and estimated total numbers of EV-A71 and CV-A16. RESULTS: There were more HA events (4.0 millions) than HFMD events (1.2 millions) in Taiwan. In every 1000 events with HFMD and HA, 6.0 and 4.1, respectively, respiratory samples were collected. The NPEV positive rate in HFMD-related samples was 48%, consistent across most sampling seasons, and predominantly EV-A71 or CV-A16 (74%). By comparison, the HA-related samples had a lower positive rate overall (43%), occasionally EV-A71 or CV-A16 (13%), and the positive rate depended strongly on HA incidence (P < 10). Compared with sampling HFMD alone, inclusion of HA-related information predicted an earlier onset of EV-A71 outbreak in 2011, and predicted 30% more EV-A71 cases. CONCLUSIONS: This is the first representative report on viral characteristics of HA. Our findings confirm that HFMD monitoring is a reliable strategy, but there is a measurable additional benefit when HA is also monitored.

Association between maternal shift work and infant neurodevelopmental outcomes: results from the Taiwan Birth Cohort Study with propensity-score-matching analysis.

BACKGROUND: Maternal shift work is associated with preterm delivery, small-for-gestational-age new-borns, childhood obesity and future behavioural problems. However, the adverse effects on and interactions of maternal shift work with infant neurodevelopment remain uncertain. Therefore, we examined the associations between maternal-shift-work status and infant neurodevelopmental parameters. METHODS: The Taiwan Birth Cohort Study is a nationwide birth cohort study following representatively sampled mother-infant pairs in 2005. The participants' development and exposure conditions were assessed by home interviews with structured questionnaires at 6 and 18 months of age. Propensity scores were calculated with predefined covariates for 1:1 matching. Multivariate conditional logistic regression and the Cox proportional-hazards model were used to examine the association between maternal-shift-work status and infant neurodevelopmental-milestone-achievement status. RESULTS: In this study, 5637 term singletons were included, with 2098 cases selected in the propensity-score-matched subpopulation. Persistent maternal shift work was associated with increased risks of delays in gross-motor neurodevelopmental milestones [aOR = 1.36, 95% confidence interval (CI) = 1.06-1.76 for walking steadily], fine-motor neurodevelopmental milestones (aOR = 1.39, 95% CI = 1.07-1.80 for scribbling) and social neurodevelopmental milestones (aOR = 1.35, 95% CI = 1.03-1.76 for coming when called upon). Moreover, delayed gross-motor and social development were identified in the propensity-score-matched sub-cohort. CONCLUSIONS: This study shows negative associations between maternal shift work and delayed neurodevelopmental-milestone achievement in the gross-motor, fine-motor and social domains at 18 months. Future research is necessary to elucidate the possible underlying mechanisms and long-term health effects.